Abstract

Objectives: Diabetic retinopathy (DR) is associated with progressive retinal capillary activation and proliferation, leading to vision impairment and blindness. Microparticles (MPs) are submicron membrane vesicles with biological activities, released following cell activation or apoptosis. We tested the hypothesis that pro-angiogenic MPs accumulate in vitreous fluid in DR.

Research Design and Methods: Levels and cellular origin of vitreous and plasma MPs from control (n=26) and diabetic (n=104) patients were analyzed by flow cytometry and their pro-angiogenic activity assessed by in vitro thymidine incorporation and neovessel formation in subcutaneous Matrigel plugs in mice.

Results: MPs of endothelial, platelet, photoreceptor and microglial origin were identified in vitreous samples. Levels of photoreceptor and microglial MPs were undetectable in plasmas, but were comparable in diabetic and control vitreous samples. Vitreous platelet and endothelial MPs levels were increased in diabetic patients, and decreased following panretinal laser photocoagulation or intravitreal anti-VEGF injection in proliferative DR. The ratio of vitreous to plasma MPs levels was calculated to estimate local formation versus potential plasma leakage. In proliferative DR, the endothelial MPs ratio -but not that for platelet- was greater than one, indicating local formation of endothelial MPs from retinal vessels and permeation of platelet MPs from plasma. Isolated vitreous MPs stimulate by 1.6 fold endothelial proliferation and increased new vessel formation in mice.

Conclusions: The present study demonstrates that vitreous fluid contains shed membrane microparticles of endothelial, platelet and retinal origin. Vitreous MPs levels are increased in patients with diabetic retinopathy, where they could contribute to disease progression.